Long-term results from CheckMate 816 further support nivolumab plus chemotherapy as a standard neoadjuvant treatment for patients with resectable NSCLC
Long-term analysis of the phase III CheckMate 816 trial (at a median follow-up of 41.4 months) confirm that neoadjuvant nivolumab plus platinum doublet chemotherapy prolongs event-free survival (EFS) compared with chemotherapy alone. Furthermore, additional exploratory analyses reveal that EFS at three years is not influenced by surgical parameters and suggest that tumour inflammation may be a useful predictive biomarker.
In the randomised, phase III CheckMate 816 study, neoadjuvant nivolumab plus chemotherapy could demonstrate a statistically significant and clinically meaningful improvement in event-free survival (EFS) and pathologic complete response (pCR) versus chemotherapy alone in patients with resectable non-small cell lung cancer. However, there remains to be an unmet need for biomarkers to identify patients with resectable NSCLC who may derive clinical benefit from neoadjuvant or adjuvant immunotherapy. At ELCC 2023, Prof. Nicolas Girard reported on the three-year safety and efficacy results from CheckMate 816, as well as an exploratory biomarker analysis.
Adults with newly diagnosed, stage IB (tumours ≥4 cm)–IIIA (per AJCC TNM 7th edition) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK alterations were randomised to nivolumab 360 mg plus chemotherapy once every three weeks (Q3W) or chemotherapy alone (Q3W) for 3 cycles followed by surgery. Surgery was performed within six weeks post-treatment. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumour samples.
After a median follow-up of 41.4 months, a continued EFS benefit was observed with nivolumab plus chemotherapy vs. chemotherapy alone. Three-year EFS rates were higher with nivolumab plus chemotherapy versus chemotherapy (57% vs. 43%, HR[95%CI]: 0.68[0.49-0.93]). This benefit was consistent both among patients treated with minimally invasive surgery (67% vs. 53%, HR[95%CI]: 0.61[0.28-1.29]) and among those receiving thoracotomy or conversion (61% vs. 51%, HR[95%CI]: 0.74[0.48-1.13]). Three-year EFS rate improvements with nivolumab plus chemotherapy versus chemotherapy alone were also not dependent on the extent of resection (with rates of 64% vs. 49% for lobectomy and 67% vs. 48% for pneumonectomy) and were evident in patients with complete (R0) resection (with rates of 64% vs. 51%, HR[95%CI]: 0.65[0.43-0.98]). Time to distant metastases also continued to favour nivolumab plus chemotherapy vs. chemotherapy alone (median not reached vs. 34.3 months, HR[95%CI]: 0.55[0.39-0.78]). Among patients undergoing surgery, recurrence rates were 28% in those receiving nivolumab plus chemotherapy and 42% in those receiving chemotherapy alone. In patients receiving nivolumab plus chemotherapy, a baseline 4-gene inflammatory signature score was numerically higher in those achieving a pathological complete response. In addition, a high inflammatory score was linked to an improved EFS. Overall survival remained immature at this update but continued to show a promising trend favouring neoadjuvant nivolumab plus chemotherapy (HR[99.34%]: 0.62[0.36-1.05], p= 0.0124). Finally, the safety profile of neoadjuvant nivolumab plus chemotherapy was consistent with previous reports.
In this three-year analysis from CheckMate 816, neoadjuvant nivolumab plus chemotherapy showed long-term EFS benefit vs. chemotherapy in patients with resectable NSCLC. In addition, fewer patients treated with neoadjuvant nivolumab plus chemotherapy vs. chemotherapy had recurrence overall after surgery, including distant recurrence in the CNS. Finally, exploratory analyses of the 4-gene inflammatory signature suggested that high baseline tumour inflammation may be associated with improved EFS and pCR with neoadjuvant nivolumab plus chemotherapy.
Girard N, et al. Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816. Presented at ELCC 2023; Abstract 84O.